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Background <p>Non-small cell lung cancer (NSCLC) stands as a predominant contributor to cancer-related mortality, with angiogenesis serving a pivotal role in the advancement of the disease. The upregulation of LINC00323 in NSCLC has been identified; however, its function in facilitating NSCLC progression remains ambiguous. This investigation delves into the implications of LINC00323 on cellular proliferation, angiogenesis, and associated pathways in NSCLC, emphasizing its regulation of CDC5L stability and its presence within exosomes.</p> Methods <p>The expression of LINC00323 was scrutinized in NSCLC tissues and cells through RT-qPCR and FISH techniques. The influence of LINC00323 and exosomes derived from NSCLC cells with modified LINC00323 expression on cellular proliferation and angiogenesis was evaluated in A549 and H358 cell lines. Co-culture with HUVECs was employed to assess endothelial functionality. RNA pull-down assays and proteomic analyses identified CDC5L as a downstream target of LINC00323. The activation of MAPK and JAK-STAT pathways was investigated via Western blotting.</p> Results <p>The results indicated that LINC00323 was significantly upregulated in NSCLC tissues, correlating with a poorer prognosis and heightened angiogenesis. Overexpression of LINC00323 facilitated cellular proliferation and angiogenesis, while its knockdown impeded these processes. Moreover, exosomes containing LINC00323 from NSCLC cells stimulated angiogenesis and preserved endothelial barrier integrity in HUVECs. LINC00323 was shown to directly interact with and stabilize CDC5L. Functional complementation experiments demonstrated that the knockdown of CDC5L counteracted the effects of LINC00323 overexpression on cellular proliferation, angiogenesis, and the MAPK/JAK-STAT pathways in vitro. In vivo studies revealed that LINC00323 knockdown in A549 xenografts led to reductions in tumor size, angiogenesis, and the MAPK and JAK-STAT pathways, with CDC5L overexpression mitigating these effects.</p> Conclusions <p>LINC00323 within exosomes accelerates the progression of NSCLC and activates the MAPK and JAK-STAT pathways by stabilizing CDC5L. These findings underscore LINC00323 as a potential therapeutic target for NSCLC, particularly in its modulation of the angiogenesis.</p>

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Exosomal LINC00323 accelerates angiogenesis through activating the MAPK and JAK-STAT pathways by stabilizing CDC5L in NSCLC

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月27日

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  • Bin Ke,
  • Hai Zhong,
  • Xiaofei Chen,
  • Lijun He,
  • Chenxin Yan,
  • Jianjun Li,
  • Lin Shi

摘要

Background

Non-small cell lung cancer (NSCLC) stands as a predominant contributor to cancer-related mortality, with angiogenesis serving a pivotal role in the advancement of the disease. The upregulation of LINC00323 in NSCLC has been identified; however, its function in facilitating NSCLC progression remains ambiguous. This investigation delves into the implications of LINC00323 on cellular proliferation, angiogenesis, and associated pathways in NSCLC, emphasizing its regulation of CDC5L stability and its presence within exosomes.

Methods

The expression of LINC00323 was scrutinized in NSCLC tissues and cells through RT-qPCR and FISH techniques. The influence of LINC00323 and exosomes derived from NSCLC cells with modified LINC00323 expression on cellular proliferation and angiogenesis was evaluated in A549 and H358 cell lines. Co-culture with HUVECs was employed to assess endothelial functionality. RNA pull-down assays and proteomic analyses identified CDC5L as a downstream target of LINC00323. The activation of MAPK and JAK-STAT pathways was investigated via Western blotting.

Results

The results indicated that LINC00323 was significantly upregulated in NSCLC tissues, correlating with a poorer prognosis and heightened angiogenesis. Overexpression of LINC00323 facilitated cellular proliferation and angiogenesis, while its knockdown impeded these processes. Moreover, exosomes containing LINC00323 from NSCLC cells stimulated angiogenesis and preserved endothelial barrier integrity in HUVECs. LINC00323 was shown to directly interact with and stabilize CDC5L. Functional complementation experiments demonstrated that the knockdown of CDC5L counteracted the effects of LINC00323 overexpression on cellular proliferation, angiogenesis, and the MAPK/JAK-STAT pathways in vitro. In vivo studies revealed that LINC00323 knockdown in A549 xenografts led to reductions in tumor size, angiogenesis, and the MAPK and JAK-STAT pathways, with CDC5L overexpression mitigating these effects.

Conclusions

LINC00323 within exosomes accelerates the progression of NSCLC and activates the MAPK and JAK-STAT pathways by stabilizing CDC5L. These findings underscore LINC00323 as a potential therapeutic target for NSCLC, particularly in its modulation of the angiogenesis.